Core C will provide genetically characterized tissues to each of the projects and Core D. In addition they will engage in genetic discovery using genome wide exomic sequencing to find new mutations in patients whose susceptibility is unrelated to RyRI and CaV1.1. The PI is the Director of the UK MH diagnostic center that investigates more than 150 patients for MH susceptibility each year (more than 6000 in total) using muscle biopsy and in vitro contracture tests (IVCT). From experience of the last two years we anticipate that at least 50 patients each year will be susceptible and that 30-40 of these will harbor mutations in the RYRI gene. DNA and/or frozen skeletal muscle of more than 1800 susceptible individuals is available to further the aims of the overall program. Specifically Core C will: 1. Collect blood and skeletal muscle samples from patients attending for diagnosis of MH susceptibility 2. Identify molecular genetic variants associated with MH susceptibility using the following strategy: a. Screen for common mutations in RYR1 - if negative then; b. Use next-generation sequencing technology to sequence the exons of RYR1 and CACNA1S - if no mutations identified then; c. Use whole genome exon sequencing to identify genetic variants in genes other than RYRI and CACNA1S. Details of novel variants will be provided to Core B who will generate cDNA constructs for expression in appropriate cell lines to be investigated by Projects 1, 2 and 3. 3. Supply primary myoblast cultures from genotyped MHS and MHN patients to Core B for distribution to Projects 1, 2 and 3. 4. Supply human MH biopsy samples of specified genotype to Project 2 (snap frozen) for analysis of RYR1 post-translational modification and to Core D (glutaraldehyde fixed) for ultrastructural analysis. When possible findings will be compared with changes in murine models with the same genotype 5. Maintain a database that correlates clinical MH and IVCT phenotype data with genotype data to inform the program projects.